Walker J.L.,The University of Oklahoma Health Sciences Center |
Powell C.B.,Kaiser Permanente |
Chen L.-M.,University of California at San Francisco |
Carter J.,Sloan Kettering Cancer Center |
And 4 more authors.
Cancer | Year: 2015
Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer. Cancer 2015;121:2108-2120. © 2015 American Cancer Society.
Stephen T.L.,Wistar Institute |
Rutkowski M.R.,Wistar Institute |
Allegrezza M.J.,Wistar Institute |
Perales-Puchalt A.,Wistar Institute |
And 7 more authors.
Immunity | Year: 2014
Tumor-reactive Tcells become unresponsive in advanced tumors. Here we have characterized a common mechanism of Tcell unresponsiveness in cancer driven by the upregulation of the transcription factor Forkhead box protein P1 (Foxp1), which prevents CD8+ Tcells from proliferating and upregulating Granzyme-B and interferon-γ in response to tumor antigens. Accordingly, Foxp1-deficient lymphocytes induced rejection of incurable tumors and promoted protection against tumor rechallenge. Mechanistically, Foxp1 interacted with the transcription factors Smad2 and Smad3 in preactivated CD8+ Tcells in response to microenvironmental transforming growth factor-β (TGF-β), and was essential for its suppressive activity. Therefore, Smad2 and Smad3-mediated c-Myc repression requires Foxp1 expression in Tcells. Furthermore, Foxp1 directly mediated TGF-β-induced c-Jun transcriptional repression, which abrogated Tcell activity. Our results unveil a fundamental mechanism of Tcell unresponsiveness different from anergy or exhaustion, driven by TGF-β signaling on tumor-associated lymphocytes undergoing Foxp1-dependent transcriptional regulation. © 2014 Elsevier Inc.
Rutkowski M.R.,Wistar Institute |
Stephen T.L.,Wistar Institute |
Svoronos N.,Wistar Institute |
Allegrezza M.J.,Wistar Institute |
And 11 more authors.
Cancer Cell | Year: 2015
The dominant TLR5R392X polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism. © 2015 Elsevier Inc.
Mulligan Jr. C.R.,Helen aham Cancer Center |
Mulligan Jr. C.R.,Alan arson Regional Cancer Center
Surgical Oncology Clinics of North America | Year: 2013
This article reviews the current management of esophageal cancer, including staging and treatment options, as well as providing support for using multidisciplinary teams to better manage esophageal cancer patients. © 2013 Elsevier Inc.
Witt R.L.,Thomas Jefferson University |
Iacocca M.,Helen aham Cancer Center
American Journal of Otolaryngology - Head and Neck Medicine and Surgery | Year: 2012
The aim of this study was to compare capsule exposure using extracapsular dissection (ECD) with partial superficial parotidectomy (PSP) for pleomorphic adenoma. Purpose: Long-term favorable results for recurrence and facial nerve function have been reported for ECD and PSP for parotid pleomorphic adenoma. Extracapsular dissection is distinguished from PSP in that the facial nerve is dissected in PSP but not in ECD. This article attempts to answer the following hypothesis: the margin of normal parotid tissue surrounding a parotid pleomorphic adenoma is less for ECD compared with PSP. Material and Methods: This is a retrospective individual case-control study. Twelve consecutive parotidectomy procedures with a final pathology report of pleomorphic adenoma were retrospectively measured for margin (the percent of capsule exposure around the tumor). In 8 highly selected patients, ECD was performed. Four parotid surgical procedures not meeting strict criteria underwent PSP and served as controls. Results: The eight patients with ECD had a mean of 80% (71%-99%) of the capsule exposed. The 4 PSP procedures had 21% (4%-50%) of the capsule exposed (P <.05). Conclusions: Extracapsular dissection results in higher capsule exposure. © 2012 Elsevier Inc.
Intenzo C.M.,Thomas Jefferson University |
Dam H.Q.,Helen aham Cancer Center |
Manzone T.A.,Helen aham Cancer Center |
Kim S.M.,Thomas Jefferson University
Seminars in Nuclear Medicine | Year: 2012
The thyroid gland was one of the first organs imaged in nuclear medicine, beginning in the 1940s. Thyroid scintigraphy is based on a specific phase or prelude to thyroid hormone synthesis, namely trapping of iodide or iodide analogues (ie, Tc99m pertechnetate), and in the case of radioactive iodine, eventual incorporation into thyroid hormone synthesis within the thyroid follicle. Moreover, thyroid scintigraphy is a reflection of the functional state of the gland, as well as the physiological state of any structure (ie, nodule) within the gland. Scintigraphy, therefore, provides information that anatomical imaging (ie, ultrasound, computed tomography [CT], magnetic resonance imaging) lacks. Thyroid scintigraphy plays an essential role in the management of patients with benign or malignant thyroid disease. In the former, the structure or architecture of the gland is best demonstrated by anatomical or cross-sectional imaging, such as ultrasound, CT, or even magnetic resonance imaging. The role of scintigraphy, however, is to display the functional state of the thyroid gland or that of a clinically palpable nodule within the gland. Such information is most useful in (1) patients with thyrotoxicosis, and (2) those patients whose thyroid nodules would not require tissue sampling if their nodules are hyperfunctioning. In neoplastic thyroid disease, thyroid scintigraphy is often standard of care for postthyroidectomy remnant evaluation and in subsequent thyroid cancer surveillance. Planar radioiodine imaging, in the form of the whole-body scan (WBS) and posttherapy scan (PTS), is a fundamental tool in differentiated thyroid cancer management. Continued controversy remains over the utility of WBS in a variety of patient risk groups and clinical scenarios. Proponents on both sides of the arguments compare WBS with PTS, thyroglobulin, and other imaging modalities with differing results. The paucity of large, randomized, prospective studies results in dependence on consensus expert opinion and retrospective analysis with inherent bias. With a growing trend not to ablate low-risk patients, so that a PTS cannot be performed, some thyroid carcinoma patients may never have radioiodine imaging. In routine clinical practice, however, imaging plays a critical role in patient management both before and after treatment. Moreover, as evidenced by the robust flow of publications concerning WBS and PTS, planar imaging of thyroid carcinoma remains a topic of great interest in this modern age of rapidly advancing cross sectional and hybrid imaging with single-photon emission computed tomography, single-photon emission computed tomography/CT, and positron emission tomography/CT. © 2012 Published by Elsevier Inc.
Simonelli L.E.,Helen aham Cancer Center
Delaware medical journal | Year: 2010
There is a relative sparsity of research on and resources for individuals with and survivors of gynecologic cancer compared to other cancers. This paper aims to review the current literature related to the challenges this population faces and subsequent support needs. In addition, it discusses future steps that will allow for the highest quality of care for those recovering from gynecologic cancers.
Heinberg L.J.,Case Western Reserve University |
Keating K.,John Carroll University |
Simonelli L.,Helen aham Cancer Center
Obesity Surgery | Year: 2010
Background: Patients choose to undergo bariatric surgery for a variety of medical and psychosocial reasons. However, the majority of bariatric surgery candidates have unrealistic weight loss goals, and certain subgroups within this population may be more likely to endorse such beliefs. This study examines weight loss expectations in patients undergoing three different weight loss procedures (laparoscopic Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or laparoscopic sleeve gastrectomy). Methods: Between October 2007 and June 2008, 114 patients (81.6% female) underwent weight loss surgery. At entry into the program, patients identified their postsurgical goal weights. "Realistic" weights were calculated based on patients' presurgical excess weights and expected loss based upon their surgical procedure. Results: Patient [mean preoperative body mass index (BMI)=48.89] weight loss discrepancies were quite variable with "realistic" versus "dream" weight discrepancies ranging from 0.34 to 71.11 kg (M=28.79 kg; SD=13.21 kg). The mean was equivalent to losing 106% (SD=0.15%) of excess body weight. Baseline BMI, female gender, younger age, and Caucasian ethnicity accounted for up to 62% of the variance in discrepancy scores. After controlling for initial BMI, there were no differences in discrepancies based upon type of surgery. Conclusions: Across all three surgery types, women, Caucasians, younger patients, and those with higher initial BMIs were more likely to have unrealistic goals. Informed consent procedures should help patients, particularly those most likely to be unrealistic, understand likely outcomes as part of education on risks and benefits of weight loss surgery. © 2009 Springer Science + Business Media, LLC.
Witt R.L.,Helen aham Cancer Center
The Laryngoscope | Year: 2016
OBJECTIVES/HYPOTHESIS: Gene expression classifiers can safely reduce diagnostic thyroid surgery for fine-needle aspiration cytology (FNAC) indeterminate thyroid nodules.STUDY DESIGN: Retrospective review, single-institution, single-practice surgeon.METHODS: Three-year retrospective review of indeterminate FNAC that went on to gene expression classifier testing.RESULTS: A total of 520 patients met American Thyroid Association guideline criteria for surgeon-performed ultrasound-guided FNAC for a thyroid nodule with on-site cytopathology. The indeterminate (Bethesda III or IV) FNAC rate was 9%. Prevalence of malignancy in FNAC indeterminate was 21%. Thirty-two cases went on to gene expression classifier testing. Fourteen were benign, 15 suspicious, and three with no result.CONCLUSIONS: Benign gene expression classifier testing had an estimated negative predictive value of 100% during the study period. These patients have been observed for a mean and median duration of 14 and 7 months, respectively. In this small series, 14 of 29 patients with indeterminate FNAC were spared diagnostic surgery.4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
Denstman F.,Helen aham Cancer Center
Surgical Oncology Clinics of North America | Year: 2014
At initial presentation, 20% to 30% of patients with colon and rectal cancer have detectable metastatic disease. Precise guidelines are lacking for the treatment of this special subset. Most of these patients have only hepatic metastases. Treatment recommendations for these stage 4 patients must take into account characteristics of the primary tumor, the potential resectability of the metastatic disease, and the proper role of chemotherapy and radiation therapy. Because of the tremendous variability of these characteristics, recommendations must be individualized. This article is a basic approach to the treatment of these patients. © 2014 Elsevier Inc.